This is an application for a renewal of Mid-Career Investigator Award in Patient Oriented Research (K24) Biological Correlates of Traumatic Stress for J. Douglas Bremner, M.D., to allow him to continue to provide mentoring to junior investigators in the area of biological correlates of traumatic stress. Studies by the applicant have applied brain imaging to the study of posttraumatic stress disorder (PTSD), using magnetic resonance imaging (MRI) to show smaller hippocampal volume in PTSD, and positron emission tomography (PET) to show alterations in a neural circuit involving medial prefrontal cortex, hippocampus and amygdala in PTSD. Other studies by the applicant applied animal findings showing that serotonin reuptake inhibitors (SSRIs) promote neurogenesis (which is inhibited by stress) to show that SSRIs result in a 5% increase in hippocampal volume and 30% improvement in hippocampal-based declarative memory function. Current studies are using imaging to study neural correlates of response to treatment in PTSD and neural and myocardial correlates of stress and depression. The applicant has been very productive in performing research and has mentored 43 trainees during his early career and in the first period of this K24 in conjunction with his T32 Training Program in Neuroimaging Sciences (TPINS). The Training Program in Neuroimaging Sciences (TPINS), Graduate Program in Neuroscience at Emory, and other resources, including the Center for Disease Control (CDC), Center for Behavioral Neuroscience, and Yerkes Regional Primate Center, represent excellent opportunities for research and the development of trainees. There is a collegial and collaborative atmosphere at Emory that creates as excellent experience for trainees. Emory University has the highest proportion of minority students and faculty of any of the top 25 universitites in the US, offering an excellent opportunity for training in an area particularly relevant for minorities. The mentorin provided by the applicant will provide an important new crop of investigators to conduct the next generation of research in the field of biological correlates of traumatic stress. PUBLIC HEALTH RELEVANCE: Traumatic stress is an important and pervasive public health concern, with early traumas such as childhood abuse leading to long-term negative effects on mental and physical health. The current program provides mentoring for trainees from a variety of backgrounds, including physicians and junior scientists, to train in the area of biological correlates of traumatic stress. This highly productive program of research and training offers to provide important findings in the field of biological correlates of traumatic stress, as well as to furnish the next generation of scientists and research physicians who will make important contributions to this field in the future. The program holds promise for the advancement of the treatment of patients suffering from mental and physical health correlates of exposure to traumatic stress.